Friday, May 31, 2013

For those awaiting changes in the treatment of hepatitis C, it's almost time to toss the confetti. The field is on the verge of one of the most profound upgrades in any therapeutic category, promising real progress in efficacy, tolerability and convenience. Barring any safety bombshells, a prolific pipeline of direct-acting anti-viral agents (DAAs) is due to start issuing forth options that, when combined, will permit all-oral, interferon-free treatment.

By making future HCV treatment shorter, safer, easier and more effective, says Jonathan Fenkel, MD, director of the hep. C center at Thomas Jefferson University, these protocols “will open the door to many more patients who have declined or deferred treatment.”

That could mean billions in sales. Analysts say new therapies could help grow the pie for the virus to $20 billion annually by 2020. The infectious diseases market, as a whole, rose from $33.6 billion in 2011, to $35.2 billion in 2012, according to data compiled by IMS Health on sales of hep. C and HIV drugs, as well as antibiotics and vaccines.

Clinicians and analysts agree that the first and likely go-to therapy will eventually be Gilead Sciences' sofosbuvir (GS-7977). Gilead has applied for approval of sofosbuvir and ribavirin as an all-oral therapy for patients with genotypes 2 and 3—the minority of patients with hep. C in the US (about 75% of patients are genotype 1).

Gilead's agent is the “holy grail of HCV treatment,” analyst Julie Hoggatt tells MM&M. The first hep. C drug to cut treatment duration to 12 weeks, vs. 24 weeks with the available DAAs (Vertex's Incivek or Merck's Victrelis), it boosts efficacy from a 70% cure rate to over 80%. Phase II data from Gilead suggest a further 33% reduction in treatment duration—from 12 weeks down to eight—in patients taking a combination of sofosbuvir and Gilead's ledipasvir, aka GS-5885.

The nucleotide analogue polymerase inhibitor (or “nuc”) has broad-spectrum genomic activity (meaning that it covers multiple hep. C genotypes), a barrier to the development of viral resistance, has once-daily dosing, and can be co-formulated with other agents.

Other players include AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Merck, Vertex and smaller biotechs. Some could find a niche among the difficult-to-treat population. But, says Hoggatt, a principal with Symphony Health Solutions' inThought Research, “We are forecasting Gilead to be the clear majority player, with sofosbuvir capturing 75% peak market share.” She predicts approval as early as mid-December for use in genotypes 2 and 3. By 2015, sofosbuvir's label is likely to be expanded as part of an all-oral regimen for the more common genotype 1, when combined with ledipasvir.

In the meantime, in Thought expects some off-label use of sofosbuvir plus ribavirin without interferon in treatment-naïve genotype 1 patients, the analyst wrote in an April research note in which she modeled peak worldwide sales of $4.3 billion for sofosbuvir. This is a conservative forecast, below street consensus which is over $7 billion.

“Shortening treatment and lowering the pill burden will have a huge effect on compliance, efficacy, and acceptance,” says Jefferson's Fenkel. Not to mention safety: IMS analyst Steve Gubernick notes, “You don't have to worry about paying for side effects anymore.”

This is a wholesale transformation from today's standard of care, which incorporates pegylated interferon (PEG-IFN), ribavirin and a protease inhibitor (Incivek or Victrelis). Many of today's HCV treaters are holding patients back until the new wave of oral medication hits.

According to Hoggatt and others, the next most-dominant company in the HCV market after Gilead will likely be AbbVie, whose multi-drug oral regimen has high efficacy among null responders. It scored FDA's “breakthrough” status, as did BMS hep. C drug daclatasvir.

In testing, daclatasvir with asunaprevir and BMS-791325, produced a high cure rate in prior treatment failures. And BI presented data on NS3/4a protease inhibitor faldaprevir which, in conjunction with pegylated interferon and RBV, had a 79-80% rate of cure in a group that had a high proportion of tough-to-treat cirrhotic patients.

Hep. C is, for most patients, not fast-moving, so they can wait for new options. In a research note, ISI Group analyst Mark Schoenebaum, MD, estimated that around 350,000 US patients are under the care of a hep. C specialist and can be easily accessed and activated once new treatments arrive. The challenge is getting patients diagnosed and into the medical system; and, once they are, managing the potential flood of treatment-eligible patients. There are about three million infected patients in the US, four million in Western Europe, about a million in Japan and seven million in Eastern Europe.

Another caveat: Who'll pay for the new regimens, which could cost $100,000 or more for a three-month course. While today's regimens cost from $65,000-$80,000, according to ISI's Schoenebaum, “I [w]ould be very surprised if [sofosbuvir] were priced significantly less than $80k, and wouldn't be shocked to see $100k.” inThought's Hoggatt models a wholesale cost closer to $54,000 for a 12-week course.

What is dictated by the payers will be important. “If we have equal efficacy and side-effect profiles for all of the regimens, the payers may have preferences,” says Paul Pockros, MD, division head of gastroenterology and hepatology at the Scripps Clinic in San Diego. Of course, all of this new drug excitement is unfolding against the backdrop of ObamaCare, rolling out in 2014. That means more people covered, but leaves guesswork as to the span of pharmaceutical coverage.

While a revolution is under way in hep. C, in HIV/AIDS it's more of an evolution. With the approval of Gilead's quad-pill Stribild, there are three one-pill, once-a-day, single-tablet regimens available, all with high efficacy and favorable tolerability. Attention is focused mostly on the safest, most convenient way to treat patients chronically for life.

“Our focus is still on the safest regimens that give patients a healthy lifespan without cumulative toxicities,” says Cal Cohen, MD, a leader in HIV research and an instructor at Harvard University. Cohen spotlights two investigational anti-retroviral medications in the pipeline. Gilead's tenofovir alafenamide fumarate (TAF; GS-7340) has so far shown greater antiviral activity with potentially fewer concerns about kidney function or bone mineral density. The other investigational agent Cohen's eying is ViiV's second-generation integrase inhibitor dolutegravir, which has demonstrated sustained efficacy and once-daily dosing, without the need for a pharmacokinetic booster.

CLINICAL CORNER

The days of interferon are numbered. So, what are the next important milestones in the evolution of hepatitis C drug development? The two next big signposts, sources say, are the removal of ribavirin from treatment protocols as well as the further truncating of HCV regimens to as short as eight weeks, down from today's 24-48.

Ribavirin is a double-edged sword. It has been shown to reduce the rate of relapse and it's cheap. But it's a weak anti-viral whose mechanism of action against HCV is not well understood, and it's dosed twice daily. RBV, as it's known, also brings such side effects as anemia, so physicians can't dose it in patients with kidney impairment, and teratogenicity (a contraindication in pregnant women).

The latter “complicates recruiting women of child-bearing age into clinical trials—a substantial number of HCV patients!” says Wayne Dankner, MD, global therapeutic area lead for infectious diseases and pediatrics with the CRO Parexel. It also affects male subjects as they must “practice adequate birth control with their female partners,” he adds.

Multiple strains of evidence from the clinical literature suggest that it may be possible to show ribavirin the door. Manufacturers like Gilead, AbbVie and Bristol-Myers Squibb are trying to identify other direct-acting anti-virals that can replace RBV in the regimen or to find agents that are sufficiently robust to obviate the need for it altogether.

The other opportunity on the horizon is to reduce the duration of therapy—an opportunity highlighted by the announcement of Gilead's Phase II Lonestar data in early May. Lonestar demonstrated a 95-100% cure rate after eight weeks of therapy with a fixed dose combination of Gilead's nuc sofosbuvir plus the NS5a ledipasvir (GS-5885).

“While most of these regimens are 12 weeks in duration, there is a continual focus on whether we can shorten to eight weeks. That would improve acceptance and lessen exposure to drugs,” says Dankner.

Another important future development is providing effective therapy to patients with more advanced liver disease, such as cirrhosis, and those with multiple co-morbidities, including HCV/HIV co-infection. Such patients have historically been much more difficult to treat.

“Enrollment of a population representative of the disease being treated is critically important,” says Peter Piliero, MD, Boehringer Ingelheim VP, clinical development and medical affairs. Other typical patient characteristics, Piliero adds, include those with both HCV genotype 1 subtypes (1a and 1b) and the various IL28b polymorphisms.

But scientists looking for new HCV treatments are not starting from scratch. Most of the companies in the field have cut their teeth developing antiretroviral agents for HIV. “We'll have a second generation of agents coming right on the heels of the first generation,” says UCSD School of Medicine's Bob Gish, MD, chief of clinical hepatology and professor of clinical medicine. “The warp speed we're seeing is because of that historical experience in other viral illnesses.”From the June 2013 Issue of MMM

GileadSciences (GILD) announced on May 21, 2013
that the European regulator EMA (European Medicines Agency) started the process
of assessing the company's once daily oral treatment for hepatitis C virus (HCV)
and will furnish an accelerated review.

Earlier, on May 13, Johnson&Johnson's (JNJ) experimental drug, still in
mid-stage trial, got priority review status from the FDA. A week earlier, the FDA
accorded breakthrough status to the Hepatitis C virus regimen of
AbbVie (ABBV).

Janssen Infectious Diseases-Diagnostics BVBA (Janssen) announced today that the European Commission (EC) has approved a new twice daily (BID) dosing of INCIVO® (telaprevir), a direct acting antiviral (DAA) protease inhibitor, in combination with pegylated-interferon and ribavirin (PR) for naive and previous treatment experienced patients. The newly approved dosing regimen for INCIVO® is now 1,125 mg twice daily in combination with PR, which aligns a morning and evening dose to the already twice daily dosing schedule for ribavirin versus 750 mg every 8 hours in combination with PR.

The EC approval is based on results from OPTIMIZE, a randomized, open-label, multicenter Phase III study in treatment naive patients with genotype-1 chronic HCV infection, which demonstrated that twice daily dosing of INCIVO® 1,125mg in combination with PR was non-inferior to the previously approved dosing every 8 hours in the proportion of patients who achieved sustained virologic response (74% versus 73%).[2] Twice daily dosing also showed similar cure rates with twice daily or every 8 hours INCIVO dosing in patients with cirrhosis.[3]

"The approval of INCIVO® twice daily is good news for patients with genotype-1 chronic HCV infection. Making treatments more simple and easier to manage, without compromising efficacy, will help to increase adherence and give patients an even greater chance of achieving a cure," said Dr Maria Buti, Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain.

The availability of new DAAs like telaprevir has transformed treatment options for HCV.[4] Telaprevir has already played a significant role in improving treatment outcomes with more than 80,000 patients treated with telaprevir combination therapy worldwide since it was first approved in 2011.[5] It also offers the shortest total treatment duration of any available HCV therapy, for a high proportion of treatment-naïve or relapse patients.[6],[7]

"Before the availability of direct acting antivirals like telaprevir, the best clinicians could hope for was to cure only 40-50% of our genotype-1 HCV patients. DAAs now offer us the chance to cure approaching 80% of these patients, for many in a shorter amount of time.Successful treatment is effectively a cure and causes a massive reduction in the complications of HCV, such as liver cancer and cirrhosis. As with many diseases early therapy is most effective and has the greatest impact on complications.The twice daily dosing of telaprevir makes the treatment easier to administer and will make it easier for patients to take advantage of the opportunity for a cure. We now need to ensure that patients with HCV are identified and offered therapy, before their disease progresses," said Graham Foster, Consultant Hepatologist, Barts Health London.

"We are pleased by the European Commission approval of twice daily dosing for telaprevir, which marks an improvement on an already important treatment option for HCV. This medicine is the cornerstone of our efforts to improve the lives of more people living with HCV and supporting healthcare professionals around the world," said Gaston Picchio, Hepatitis Disease Area Leader at Janssen.

Telaprevir was first approved by the U.S. Food and Drug Administration (FDA) in May 2011, marketed by Vertex Pharmaceuticals under the brand name INCIVEK[TM], and by the European Commission in September 2011, marketed by Janssen Pharmaceutical Companies under the brand name INCIVO®.

About OPTIMIZE

740 naïve patients chronically infected with genotype-1 HCV were treated with either a twice daily dosing of INCIVO 1,125 mg or dosing every 8 hours of INCIVO 750 mg, each in combination with PR. At Week 12, telaprevir treatment ended and patients continued on PR alone for an additional 12 or 36 weeks depending on their viral response at Week 4. Patients were evaluated 12 weeks after treatment ended (SVR12) to monitor sustained virological response (SVR) rates.[2]

The SVR12 rate for the twice daily group was 74%(274/369) compared to 73% (270/371) in the every 8 hour group with 95% confidence interval of the difference: -4.9%, 12.0%. The lower limit of the 95% CI (-4.9%) was greater than the pre-determined non-inferiority margin of -11% and therefore the non-inferiority of twice daily group over every 8 hour group was demonstrated.[7]

About INCIVO® (telaprevir)

INCIVO® (telaprevir), in combination with peginterferon alfa and ribavirin (PR), is indicated for the treatment of genotype-1 chronic HCV in adult patients with compensated liver disease (including cirrhosis) who are treatment naïve, and who have previously been treated with interferon alfa (pegylated or non pegylated) alone or in combination with ribavirin, including relapsers, partial responders and null responders.[7] INCIVO® is a small molecule, selective inhibitor of the HCV serine protease, and a member of the new class of medicine for the treatment of genotype-1 chronic HCV, direct acting antivirals (DAAs). Unlike previous treatments, DAAs act directly on viral enzymes and prevent the virus from replicating. INCIVO® was approved by the European Commission on the 19th September 2011.

INCIVO, 1,125mg (three 375mg film-coated tablets) should be taken orally twice daily (BID) with food. Alternatively, 750mg (two 375mg tablets) can be taken orally every 8hours (q8h) with food. The total daily dose is 6tablets (2,250mg).[7]

Telaprevir was developed by Janssen Infectious Diseases-Diagnostics BVBA, one of the Janssen Pharmaceutical Companies, in collaboration with Vertex Pharmaceuticals Incorporated (Vertex) and Mitsubishi Tanabe Pharma Corporation (Mitsubishi Tanabe Pharma). Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK[TM]. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries where it is being marketed as TELAVIC®.

Important Safety Information

Please see full Summary of Product Characteristics or visit http://www.emea.europa.eu for more details.

The overall safety profile of telaprevir is based on the Phase II/III clinical development programme containing 3,441 patients who received a telaprevir based regimen. In clinical trials, the incidence of adverse events of at least moderate intensity was higher in the telaprevir group than in the placebo group (both groups receiving peginterferon alfa and ribavirin). The most frequently reported adverse reactions (incidence ≥ 5.0%) of at least grade 2 in severity were anemia, rash, pruritus, nausea, and diarrhoea during the telaprevir treatment phase, and the most frequently reported adverse reactions (incidence ≥ 1.0%) of at least Grade 3 were anemia, rash, thrombocytopenia, lymphopenia, pruritus, and nausea.[7] INCIVO® prescribing information includes special warnings and pre-cautions for use with regards to rash including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Stevens - Johnson syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), where INCIVO, peginterferon alfa and ribavirin should be immediately and permanently discontinued and a specialist in dermatology consulted.[7] In cases of mild and moderate rash discontinuation of INCIVO® is not always required and patients are advised to consult with a healthcare professional. In cases of severe rash immediate discontinuation of INCIVO® is required and consultation with a specialist in dermatology is recommended.[7]

Rash events were reported in 55% of patients with a telaprevir based regimen compared to 33% of patients treated with peginterferon alfa and ribavirin only and more than 90% of rashes were of mild or moderate severity. Severe rashes were reported with telaprevir combination treatment in 4.8% of patients. Rash led to discontinuation of telaprevir alone in 5.8% of patientsand 2.6% of patients discontinued telaprevir combination treatment for rash events compared to none of those receiving peginterferon alfa and ribavirin.[7]

Hemoglobin values of < 10 g/dl were observed in 34% of patients who received telaprevir combination treatment and in 14% of patients who received peginterferon alfa and ribavirin. In placebo-controlled Phase 2 and 3 trials, 1.9% of patients discontinued telaprevir alone due to anemia, and 0.9% of patients discontinued INCIVO combination treatment due to anemia compared to 0.5% receiving peginterferon alfa and ribavirin.[7]

About HCV

Hepatitis C (HCV) is a contagious liver disease which is spread through blood-to-blood contact and is usually symptomless at the outset.[8] With an estimated 150 million people infected worldwide,[9] and three to four million people newly infected each year, HCV puts a significant burden on patients and society.[10] Estimations indicate that HCV kills more than 350,000 people worldwide per year, accounting for approximately 1% of deaths worldwide.[9] It is the world's primary cause of cirrhosis and liver cancer[11] with an estimated 20-30% of patients developing liver cirrhosis[12] and a further 7% developing liver cancer.[13] The estimated annual cost of HCV (medical and work loss) is more than $1 billion in the U.S. alone.[14]

About Janssen

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in infectious diseases and vaccines, oncology, immunology, neuroscience, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Please visit http://www.janssenrnd.com for more information.

“Hepatitis
C is a complex disease and there is a need for multiple treatment
options. Future hepatitis C treatment will be interferon free and will
consist of two to three direct acting antivirals (DAAs). We are pleased
and looking forward to having simeprevir evaluated in this
two-direct-acting antiviral phase II study”, said Charlotte Edenius, EVP
Development, Medivir AB.

About the HELIX trial
The HELIX-1
trial is a 12-week, randomized, double-blind, parallel group study
evaluating the safety and tolerability of simeprevir and samatasvir in
addition to antiviral activity endpoints, with a target enrollment of 90
treatment-naïve, non-cirrhotic, genotype 1b or 4 HCV-infected patients.

The HELIX-1 trial is the first
study in HCV-infected patients to commence under a non-exclusive
collaboration agreement signed between Janssen and Idenix in January
2013. A second trial (HELIX-2) of simeprevir, samatasvir and TMC647055, a
once-daily non-nucleoside polymerase inhibitor boosted with low-dose
ritonavir being developed by Janssen, is expected to commence in the
second half of 2013.

About Simeprevir
Simeprevir
is an investigational NS3/4A protease inhibitor jointly developed by
Medivir AB and Janssen R&D Ireland for the treatment of genotype 1
chronic hepatitis C in adult patients with compensated liver disease,
including all stages of liver fibrosis. Simeprevir works by blocking the
protease enzyme that enables the hepatitis C virus to replicate in host
cells.

New drug applications were recently submitted for
simeprevir in Japan and the United States for the treatment of genotype 1
hepatitis C, and a Marketing Authorisation Application was submitted to
the European Medicines Agency seeking approval of simeprevir for the
treatment of genotype 1 or genotype 4 chronic hepatitis C. The U.S. FDA
has granted Priority Review to the New Drug Application.

Global
phase III studies of simeprevir include PROMISE in adult patients who
have relapsed after prior interferon-based treatment, QUEST-1 and
QUEST-2 in treatment-naïve adult patients, and ATTAIN in prior
null-responder adult patients. In parallel to these trials, phase III
studies for simeprevir are ongoing in treatment-naïve and
treatment-experienced HIV-HCV co-infected patients and HCV genotype 4
patients.

Simeprevir is also being studied in phase II interferon-free trials with and without ribavirin in combination with:

In addition, Janssen Pharmaceuticals, Inc. has
entered into a non-exclusive collaboration with Vertex Pharmaceuticals
to evaluate in a phase II study the safety and efficacy of an all-oral
regimen of simeprevir and Vertex’s investigational nucleotide analogue
polymerase inhibitor VX-135 for the treatment of HCV. As a first step,
Janssen Pharmaceuticals, Inc. is conducting a drug-drug interaction
(DDI) study with simeprevir and VX-135.

About Samatasvir (IDX719)
Samatasvir
is an NS5A inhibitor with low picomolar, pan-genotypic antiviral
activity in vitro. To date, samatasvir has been safe and well-tolerated
after single and multiple doses of up to 150 mg in healthy volunteers
for up to 14 days duration and up to 100 mg in HCV-infected patients for
up to 3 days duration.

There have been no treatment-emergent
serious adverse events reported in the program. Samatasvir has
demonstrated potent pan-genotypic antiviral activity in HCV-infected
patients with mean maximal viral load reductions up to approximately 4.0
log10 IU/mL across HCV genotypes 1-4 in a proof-of-concept, three-day
monotherapy study. For information about Idenix, please refer to www.idenix.com.

About Hepatitis C
Hepatitis
C, a blood-borne infectious disease of the liver and a leading cause of
chronic liver disease and liver transplants, is a rapidly evolving
treatment area with a clear need for innovative treatments.
Approximately 150 million people are infected with hepatitis C virus
worldwide, and about 350,000 people per year die from the disease. When
left untreated, hepatitis C can cause significant damage to the liver
including cirrhosis. Additionally, hepatitis C may increase the risk of
developing complications from cirrhosis, which may include liver
failure.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases.

Medivir
has world class expertise in polymerase and protease drug targets and
drug development which has resulted in a strong infectious disease
R&D portfolio. The Company’s key pipeline asset is simeprevir, a
novel protease inhibitor in late phase III clinical development for
hepatitis C that is being developed in collaboration with Janssen
R&D Ireland. Medivir has also a broad product portfolio with
prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com

Hepatitis C drugs like Gilead Sciences Inc.’s sofosbuvir, which analysts forecast will become the company’s top-seller, may spawn compulsory generics in countries that can’t afford them, according to a report backed by billionaire Richard Branson.

While health officials are negotiating with drugmakers including Gilead over the price of new medicines for the deadly liver virus, developing nations should issue so-called compulsory licenses for the therapies if price reductions aren’t sufficient, according to the report by the Global Commission on Drug Policy, of which Branson and former Federal Reserve Chairman Paul Volcker are members.

Under a World Trade Organization agreement known as trade- related aspects of intellectual property rights, or TRIPS, member countries can give licenses to generic-drug makers to make low-cost copies of treatments protected by patents that are needed to address a public health emergency.

“If the prices were to be unaffordable once more in history, it would be one more scandal around inequity of access to health care,” Michel Kazatchkine, the United Nations Secretary General’s Special Envoy on HIV/AIDS in Eastern Europe and Central Asia, said at a briefing in Geneva Thursday.

“There’s no reason why a country like Ukraine wouldn’t go for this and declare a public emergency.” Liver Damage About 170 million people are infected with hepatitis C, which is transmitted commonly among drug users who share contaminated needles, and can cause liver damage and cancer.

Of 16 million people estimated to inject drugs globally, about 10 million have hepatitis C, according to Thursday’s report, which didn’t specifically name sofosbuvir.

Spokeswomen for Gilead didn’t immediately respond to a call and e-mail requesting comment sent outside regular business hours.

Gilead applied for U.S. regulatory approval of sofosbuvir last month, and the drug may cost as much as $100,000 per patient, according to Mark Schoenebaum, an analyst at ISI Group in New York. The Foster City, California-based company gained the drug with its $11.1 billion acquisition of Pharmasset Inc. last year.

The pill may earn Gilead almost $4 billion in 2015 and $6.3 billion the following year, according to the average analyst estimates compiled by Bloomberg.

Hearing the words "you have hepatitis C" is a traumatic
and devastating moment in anyone’s life.

When diagnosed with a chronic illness many people find
themselves, scared, lost, and confused. Receiving such news is akin to having
one’s sense of self-security, mortality even, tossed into the center of a
complex maze. Through a fog of anxiety and doubt, one ever so cautiously
maneuvers around difficult decisions, desperately searching for a safe,
glorious exit.

At some point in time, you begin to ask yourself a few
questions; what can I do to improve my condition? Can this disease be treated,
if so, should I start treatment immediately or wait? Self-reflection is the
starting point of this labyrinth. Eventually one discovers the paths that lead
to acceptance and self-advocating. Hopefully, scouting these routes will make
traversing the management and treatment of the illness easier.

With this in mind, we visit the story of one such man who
made his way out of the pitfalls of chronic illness. In the fall of 2008 Don
Crocock was diagnosed with hepatitis C. Today, Don shares his story, his
trials, and the discoveries he’s made during his own journey through treatment
on the path to wellness.

Don, now sixty, takes pride in his two sons and the
life he shares with his wife Laurie in southern Ontario. Surpassing many milestones over the
course of his life, his recovery from cocaine and alcohol addiction began on
February 15th, 1993. Today, Don credits his wife with saving his life, this
year the couple celebrate twenty years of recovery.

Don is part of the baby boomer generation, which is anyone
born between 1945 and 1965. In the United States, 4 million Americans are
infected with hepatitis C, one in 30 are baby boomers and 75 percent are
unaware they have the virus. In 2012 the CDC released the recommendation that all
baby boomers should be
tested one time for hepatitis C. Recently, the Canadian Liver
Foundation (CLF) extended the recommendation for testing beyond the
boomer generation to those born between 1945 and 1975, taking into account
immigration from countries where hepatitis C is more common.

According to the CDC , 55% of persons
ever infected with HCV reported an exposure risk of either (IV drug use or
blood transfusion before July 1992), and the remaining 45% reported no known
exposure risk (CDC, unpublished data, 2012).

Other potential exposures include ever having received
chronic hemodialysis, being born to an HCV-infected mother, intranasal drug
use, acquiring a tattoo in an unregulated establishment, being incarcerated,
being stuck by a needle (e.g., in health care, emergency medical, home, or
public safety settings) and receiving invasive health-care procedures (i.e.,
those involving a percutaneous exposure, such as surgery before implementation
of universal precautions).

In Don’s case, he contracted hep C through experimental drug
use during his youth. Don is not alone, as many people today contracted the
illness the same way. Awareness for intravenous drug use during Don’s
adolescence was much lower than it is today. Also, tolerance of drug
exploration was much higher in many circles during that era.

Don offers a unique perspective on the guilt and
stigma; that for many people infected with this disease are all too familiar
with. I share with you his words of wisdom.

"People struggle with guilt and shame issues in early
recovery. It's even worse if you add in hepatitis C. We can't let our past
dictate today!"

Don was shocked when he was diagnosed, it came out
of nowhere - the mistakes of his younger self had come back to haunt
him. At the time, Don had fifteen years of recovery under his belt; he was
working as an addiction counselor and advocate. During an earlier interview Don
remarked;

“I worked so long and so hard to undo the damage from my
past, I advocated, I volunteered – and for what? It seemed like I just got
blindsided.”

In 2008 Don started to notice the first symptoms
of debilitating fatigue. Laurie became concerned, she had seldom seen her
husband nap after work, and so, she insisted Don go see a doctor. That
September it all began, the first test, the worry, the waiting. Finally, the
results were in. Don was about to hear those three words, "You have
hepatitis C."

In June 2009 while still working two jobs, Don began 48
weeks of treatment with Pegintron and Ribavirin. Faced with fibrosis, and the
knowledge that genotype 1 was the most difficult to treat, he was once again
determined to beat the odds.

Until 2011, standard therapy for hepatitis
C consisted of pegylated interferon and ribavirin. The SVR rate, or cure,
was approximately 40–50% for genotype 1 patients and higher rates of up to
80% for alternate genotypes. In May of 2011 the FDA approved Boceprevir
and Telaprevir for genotype 1 patients, the first two direct-acting antiviral agents
to treat HCV. Telaprevir increased SVR in previously untreated
genotype 1 patients to 69-75%, close to the same with Boceprevir. Both
drugs are used with Peginterferon and Ribavirin.

Don had to wait six months before beginning HCV therapy, a
protocol used by physicians for patients who have a past history of drug or
alcohol abuse. Although, in Don’s case his history dated back some fifteen
years, Don felt the blow. The stigma was alive; he had no other recourse but to
wait another six months to treat the virus.

The first viral load test came after four weeks of
treatment, it was down, but not completely gone. Don was dealing with
anemia, extreme fatigue, and many other ongoing side effects. Again his wife
stepped in and suggested a leave of absence from work. He agreed that working
both jobs had become increasingly difficult to handle. Don applied for
government employment insurance (E.I.) to cover their expenses for the next
seventeen weeks. When the insurance ended, he had twenty seven weeks left of treatment;
he worked both jobs during that time.

At week twelve Don was told his hemoglobin had dropped, he
was soon put on a rescue drug called Eprex (Procrit in the US) for thirty six weeks, one injection a week.

Then Don hit the wall, it was at week twenty six when he
felt twitching, anxiety and an overall feeling of despair.

He was sure the culprit was Ribavirin and asked his doctor
to lower the dose, but his doctor refused.

In May 2010 Don had finished treatment, coupled with the
loss of his father in the same month; Don was left feeling
exhausted and grief stricken. Refusing to give in, he decided to get some work
done around the house. Don knew he was back after painting a 120ft fence
without experiencing any of the lingering side effects which he had endured for
so long. Soon winter set in as he waited for his post PCR results. On December
8, 2010 the results were in, at last, Don was virus free!

Today Don continues working on the frontlines as an outreach worker and counselor
in Ontario.
He embraces helping others on their own roads to recovery. In 2003 Don was
awarded with the Courage to Come
Back Award from the Center for Addiction and Mental Health. He also has an
online presence, connect with Don on Facebook or Twitter.

I leave with this inspiring quote from Don;

"Acceptance allowed me to escape the "oppression of
my past" that I imposed on myself. It is what it is, and today I'm free to
be me."

Adrian Di Bisceglie, M.D., chair of internal medicine and co-director of the Liver Center at Saint Louis University, urges baby boomers to learn about the risk factors for hepatitis C and talk with their physicians about screening for the virus.

Newswise — In 1989, researchers first identified the hepatitis C virus, a health threat that had been worrying doctors as they noticed patients with unexplained liver damage occurring after receiving blood transfusions. The discovery of the potentially debilitating and deadly virus sparked several decades of productive research. Researchers made unusually rapid progress, in medical research terms, and developed therapies that had success in eliminating the virus, at least in some patients. Then, in 2011, two new drugs were brought to market that changed the landscape in a dramatic way, offering a cure for many more who suffer from a chronic form of the illness.

Currently, we estimate that 4 million people in the U.S. are infected with the virus, and at least 10,000 people in this country will die from its complications each year. Symptoms of hepatitis C can be quite variable and often only develop at the most advanced stages of liver disease, years after the virus was contracted. For this reason, it is believed that roughly 60 percent of those who have the virus are unaware of it. Patients who have a chronic infection can develop inflammation of the liver, leading to fibrosis and cirrhosis, as well as other complications that may result in liver cancer and death.

While hepatitis C is sometimes compared to HIV, and, indeed both are blood-borne, the viruses behave differently. For example, hepatitis C is not frequently spread through sexual contact. It is more likely to be transmitted from a needle stick, blood transfusion or organ transplant received before 1992, recreational drug use, or from mother to infant.

(In fact, reducing hepatitis C transmission by blood donation has been a success story of its own. In the mid-1960’s, approximately one in 10 transfusions was associated with hepatitis, initially referred to as non-A, non-B hepatitis, but now known as hepatitis C. Now, thanks to an all-volunteer blood donor system, as well as questionnaires that weed out donations from those with high risk behavior, and the routine testing of donated blood for various biomarkers of hepatitis, the risk is virtually nonexistent at one in five million.)

Today, we see hepatitis C patients from all walks of life. We see captains of industry who may have contracted the virus in their youth and healthcare workers who received accidental needle sticks on the job or even young people who acquired it from their mothers at birth. Because they may only begin to show symptoms decades later, it’s often impossible to pinpoint the exact way the virus was contracted.

However, there is an inexpensive and accurate blood test for hepatitis C. Liver disease specialists advocate that those at risk ask their doctor to be tested. In particular, the CDC now recommends that all baby boomers -- those born between 1945 and 1965 -- be screened. Doctors also urge those with risk factors such as a blood transfusion prior to 1992, a history of injection drug use and abnormal liver enzymes counts be tested.

With parallel clinical trials successfully concluding in recent years, two effective new drugs, Merck’s boceprevir and Vertex’s telaprevir, were FDA approved in 2011 to treat the virus. Added to the existing treatment regimen of peginterferon and ribavirin, these new medicines can cure nearly 80 percent of those with the disease.

Though the new treatments still require the use of peginterferon, which frequently causes taxing side effects, we’ve turned a corner. The new drugs lower the average treatment time from 1 year to 6 months. More antiviral drugs against hepatitis C are in the pipeline, and their use may eventually eliminate the need for interferon altogether.

But, right now, we can tell patients with hepatitis C that treatment time is expected to be much less than a year, is far more likely to cure them, and is likely to add years to their lives. The opportunity to halt progressive liver damage is a chance to save those with the virus from debilitating fatigue, cancer and death.

Physicians now can recommend testing to patients with the knowledge that we have effective medicines to treat the virus if we find it. These new medicines are revolutionizing the care of those with hepatitis C. It’s critical that those at risk be screened so the illness can be treated.

Adrian Di Bisceglie, M.D. is chair of the department of internal medicine and co-director of the Liver Center at Saint Louis University. He also served as Liver Diseases Section Chief at the National Institutes of Health where he supervised research in viral hepatitis and was among the first to use interferon when the illness simply was known as non-A, non-B hepatitis. Throughout the search for a cure for hepatitis C, Di Bisceglie led numerous research studies and recently co-authored a New England Journal of Medicine paper on the successful telaprevir clinical trial.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.

Video - Liver
cancer risks
Liver cancer is one of the fastest rising cancers in Canada,
but the need to educate about prevention isn't getting much attention. Kelly
Crowe explains why.

TORONTO — Ground is being gained on many fronts in the war against cancer, but one of the deadliest — liver cancer — is still on the rise, the Canadian Cancer Society said Wednesday.

About half of liver cancer cases in Canada are probably preventable, the research and advocacy organization said as it released its annual estimates of the toll cancers will exact in Canada in 2013.

Overall, the society estimates 187,600 people will learn they have a new cancer this year (excluding non-melanoma skin cancers) and 75,500 Canadians will die from some form of the disease.

The big four remain breast cancer, prostate cancer, colorectal cancer and lung cancer, but rates of these diseases are either stable or declining, says Prithwish De, a cancer epidemiologist with the cancer society.

But the same is not true for liver cancer, which currently claims the lives of four out of five people diagnosed with it. Since 1970, the incidence of liver cancer has tripled in Canadian men and doubled in women.

Primary liver cancer — as opposed to cancer that spreads from another site to the liver — is still rare. The society estimates 2,000 people will be diagnosed with it in 2013 and 1,000 people will succumb to the disease. Worldwide, liver cancer is the third leading cause of cancer deaths, after lung and stomach cancer.

The cancer is so deadly because most cases are not found until the disease has progressed beyond the point of cure. When liver cancer is found early it generally responds well to treatment, says Dr. Sean Cleary, a liver surgical oncologist at Toronto’s University Health Network.

“One of the problems with this disease is that it does not develop symptoms or patients aren’t aware that they have the problem until the disease is very advanced, at a very large and untreatable stage,” he said.

Science has made little progress improving the survival chances of people with liver cancer. Over the past 20 years, the survival rate has risen by only between two and three per cent, De says.

But the toll the disease takes could be dramatically lowered if people at high risk of developing the liver cancer took some proactive steps, experts say.

Excess alcohol consumption, obesity and diabetes are known to be risk factors for developing liver cancer. Cutting back on alcohol and taking steps to maintain a healthy weight should lower one’s liver cancer risk, they suggest.

Another way to combat the disease is by addressing two related conditions that can be precursors to liver cancer — hepatitis B and C, which are viral infections of the liver. There is currently a vaccine against hepatitis B, but none for hepatitis C.

People who are at high risk of having one or the other infection should consider talking with their doctors about being tested for hepatitis. Treatment can often clear the infections, the experts say.

“Many individuals who are infected with either acute or chronic hepatitis infections may not be aware that they’re infected. And we’re trying to let Canadians know that there is a way to get tested and find out if you are infected by either hepatitis B or C,” says De.

Last year the U.S. Centers for Disease Control urged all baby boomers to have a one-time test for hepatitis C because of the liver cancer risk. The Canadian Liver Foundation later echoed that advice.

But the Public Health Agency of Canada is studying whether it makes sense to issue a similar recommendation in Canada, where the rate of hepatitis C is lower than in the U.S. While it deliberates, the cancer society is content to wait for evidence-based advice.

“Because we’re lacking that evidence in Canada it’s kind of premature to say whether (across-the-board) screening would be beneficial to that age group,” De says.

“And so, from the Canadian Cancer Society’s perspective, we’d like to wait until there’s a good solid base of evidence before we say anything about screening in specific age cohorts.”

Instead, they recommend a discussion about screening for people who had a blood transfusion before 1990, who use or used intravenous drugs or who moved to Canada from parts of the world where hepatitis B and C are common — Asia and sub-Saharan Africa for hepatitis B, Japan and southern Europe for hepatitis C, Cleary says.

Others at risk are people who’ve had high-risk sexual contacts and received tattoos in non-reputable tattoo parlours, he said.

“Individuals who have those risk factors are definitely candidates for speaking to their doctors about finding out whether testing for hepatitis B or C and whether any other types of counselling would be beneficial for them for reducing their risk of liver cancer,” De says.

Tuesday, May 28, 2013

May 22, 2013 – By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.

With this finding, Dr. Ellis Levin and colleagues believe they are changing long-held views in the field. Study results appear in the May 21 issue of the journal Science Signaling.

“The dogma in the steroid receptor field for 50 years has been that only receptors located in the nucleus respond to steroid hormones by regulating genes that produce the developmental, functional and pathological effects of steroid hormones,” said Levin, professor of medicine, biological chemistry and pharmacology, and chief of endocrinology, diabetes and metabolism at UC Irvine and the VA Long Beach Healthcare System.

“In our study, we show that an estrogenic receptor compound acting at the cell membrane-based estrogen receptor alpha in the liver of transgenic and wild type mice suppresses all lipid synthesis. This includes cholesterol, triglycerides and fatty acids.”

Levin said this occurs through AMP kinase signaling, which inhibits the processing of the key transcription factor for many lipid-synthesis pathways genes. This causes the transcription factor to be retained in cytoplasm and prevents lipid synthesis gene expression.

“This action occurs without any participation of the nuclear receptor pool,” he added. “Thus, the membrane ER-alpha can regulate genes that produce a metabolic phenotype entirely unrelated to the nuclear receptor contributing.”

Estrogen plays a role in liver functions, and may be a deterrent to liver cancer, as men get this type of cancer at a rate of four-to-six times more than women and animals models of this cancer show clear suppression by estrogen. The hormone also helps suppress the development of fatty liver, which can lead to liver damage and failure, and inflammatory liver disease that result from chronic hepatitis.
Levin said that he and his colleagues are now testing compounds that target the membrane estrogen receptor in transgenic mice to see the impact for such diseases.

“We’re re-thinking the whole idea of hormone replacement of estrogen by exploring ways to boost estrogen receptor action selectively in a positive way,” he said. “This could include targeting one form of the receptor, or receptors at one location in cells but not all estrogen receptors.”

Last month, Levin was honored with the 2013 Solomon A. Berson Distinguished Researcher Award and Lectureship from the American Physiological Society, Endocrinology Division. The award is in recognition of Levin’s work on estrogen receptors outside the nucleus that mediates important functions of this steroid in breast cancer and the cardiovascular system, and is applicable to many other steroid receptors, including progesterone and androgen receptors in breast and prostate cancer, respectively.

Ali Pedram and Fiona O’Mahony with UC Irvine, Mahnaz Razandi with the VA Long Beach Healthcare System, and Brian J. Harvey and Harry Harvey with the Royal College of Surgeons in Dublin, Ireland, contributed to the study, which was supported by grants from National Institutes of Health (CA-100366) and the Department of Veterans Affairs Merit Review Program (ERL). O’Mahony, who is also affiliated with the VA Long Beach Healthcare System was co-funded by Marie Curie Actions, the Irish Higher Education Authority Programme for Third Level Institutions Cycle 4, and the Italian National Research Council.

Sunday, May 26, 2013

An estimated 3.2 million Americans have chronic hepatitis C, a contagious liver disease caused by the hepatitis C virus. What is particularly worrisome about this disease is that most people do not have any symptoms until the virus has caused liver damage, which can take 10 years or more. Conventional medical therapies are available, but still, some people with hepatitis C try complementary health approaches, such as dietary supplements. In fact, we know from the HALT-C study, an NIH-sponsored clinical trial, that 23 percent of the study participants were using herbal products—the most common of which was silymarin (milk thistle).

What we know from current research is that no dietary supplement has been shown to be effective for hepatitis C or its complications. NCCAM’s Web site has information on what the science says about dietary supplements, such as milk thistle, probiotics, zinc, and other supplements, for hepatitis C.

If you or a loved one has hepatitis C, I encourage you to take a look at this information. Get the facts on the research so you can be an informed consumer. And be sure to talk with your health care provider before using any dietary supplement to make certain that it is safe for you and compatible with any medical treatment you are receiving.

Take care, and as always, be well!

5 Things You Should Know About Dietary Supplements for Hepatitis C

Hepatitis C is a liver disease caused by a virus. It is usually chronic (long-lasting), but most people do not have any symptoms until the virus causes liver damage, which can take 10 or more years to happen. Without medical treatment, chronic hepatitis C can eventually cause liver cancer or liver failure. Conventional medical treatments are available for chronic hepatitis C. Some people with hepatitis C also try complementary health approaches, especially dietary supplements.

If you are considering any dietary supplement for hepatitis C, here are some things you should know.

No dietary supplement has been shown to be effective for hepatitis C or its complications.

The results of research supported by the National Institutes of Health have shown that silymarin, the active extract of milk thistle and the most popular complementary health product taken by people with liver disease, was no more effective than placebo in people with hepatitis C.

Research on other dietary supplements for hepatitis C, such as zinc, licorice root (or its extract glycyrrhizin), SAMe, and lactoferrin, is in its early stages, and no firm conclusions can be reached about the potential effectiveness of these supplements.

Colloidal silver is sometimes promoted for treating hepatitis C, but is not safe. Colloidal silver can cause irreversible side effects, including a permanent bluish discoloration of the skin.

Check with your health care provider before using any dietary supplement to make sure that it is safe for you and compatible with any medical treatment that you are receiving for hepatitis C or any other health problem.

Discussion Only
Coffee consumption has been suggested as a protective factor in the development of liver cancer, but evidence from observational studies is inconsistent.[11–25] The results of the current meta-analysis of seven prospective and nine case–control studies suggest that there is an inverse association between coffee consumption and liver cancer among different groups according to consumption level. There were significant reductions of 50% in the risk of liver cancer with the highest consumption of coffee compared with non/almost never consumption. The meta-analyses of Bravi et al.[30] found significant reductions of 55% in the risk of liver cancer with the high drinkers compared with non-drinkers, and Larsson & wolk[31] found a risk reduction of 43% per 2 cups of coffee per day increment. Our results are consistent with these two previous articles, partly because all of the studies in these two articles are included in the our meta-analysis.

Some results in this meta-analysis were heterogeneous, because the included studies had differences in study design, study region, study sex distribution, and control for confounding factors. In separate analyses by study design, we found an inverse association between coffee consumption and liver cancer among hospital- based case–control studies and among cohort studies.

There was also an inverse association between coffee consumption and liver cancer among European and Asian populations, and the significant risk reduction was stronger among Asian than European populations. The different results may be explained by racial differences. Differences in coffee drinking habits may be a partial explanation for the discrepancy.

We also found an inverse association between coffee consumption and liver cancer among male and female populations, but this result was derived from only four studies with a small number of cases, so we could not draw a firm conclusion. A history of liver disease may be a risk factor for liver cancer, and after adjustment for this, a significant inverse association remained between coffee consumption and liver cancer among two subgroups.

There are several potential mechanisms through which high consumption of coffee may reduce the risk of liver cancer. Coffee contains a variety of chemicals including caffeine, cafestol, kahweol, and chlorogenic acids. It remains uncertain which ingredient of coffee is protective against liver cancer. Some studies have indicated that caffeine can prevent oxidative DNA damage, modify the apoptotic response and reverse cell cycle checkpoint function.[32–34] Caffeine has strong antioxidant properties.[35] In an animal experiment, caffeine significantly reduced the incidence of chemically-induced hepatocellular carcinoma in rats.[36] Furthermore, cafestol and kahweol have been shown to be anti-carcinogenic.[37,38] Cafestol and kahweol have demonstrated a protective effect against aflatoxin B1-induced genotoxicity.[39] In addition, a study by Feng et al. showed that chlorogenic acids can scavenge reactive oxygen species and have an anti-tumor effect.[40] These studies suggest that ingredients in coffee may play an important role in protecting against the occurrence and development of liver cancer.

Our meta-analysis had some merits.

First, the total number of cases included in this meta-analysis was substantial (n = 3622 liver cancer cases). The summary ORs of the highest compared with the lowest coffee consumption categories for risk of liver cancer were consistent with those in a previously published meta-analyses (n = 2260 liver cancer cases).[30,31]

Second, we found little evidence of publication bias in our meta-analysis. Third, we performed a comprehensive search of the literature on the association between coffee consumption and liver cancer risk up to May 2012.

Our meta-analysis had several limitations. First, we used the highest and lowest coffee consumption levels as measures of exposure, but we were not able to determine whether different amounts of coffee consumption could decrease liver cancer risk. Second, misclassification bias should be considered. Each study presented coffee consumption in different units (cups/week, cups/day, days/week, drinks/day, times/week). Therefore, differential misclassification could bias the results.

Third, because liver cancer is a multifactorial disease, it is uncertain whether other factors may have influenced the results. Fourth, the study areas covered in our meta-analysis only included Asia (Japan, China, Hong Kong) and Europe (Finland, Greece, Italy). Therefore, the value of our results is limited for other areas (Africa, America and Australia). Fifth, potential publication bias might have influenced the results, despite no bias indicated from either the funnel plot or Egger's test.

Saturday, May 25, 2013

Two phase III studies confirm the efficacy of a sofosbuvir and ribavirin therapy in patients with HCV genotype 2 or 3 infection for whom peginterferon is not an option.

In patients infected with hepatitis C virus (HCV) genotype 2 or 3, treatment with peginterferon plus ribavirin has a sustained virologic response (SVR) of 70% to 85%. However, adverse effects of peginterferon are a barrier to treatment for many patients. Now, two industry-funded, phase III trials have evaluated the efficacy of sofosbuvir (400 mg daily) plus ribavirin (1000 mg–1200 mg daily) in these patients.

In a blinded, placebo-controlled trial, investigators randomized 280 patients for whom peginterferon therapy was not an option (e.g., adverse effects, contraindications for interferons, and patient refusal) to receive sofosbuvir/ribavirin or matching placebo for 12 weeks. In a blinded, active-control trial, researchers randomized 202 patients with prior nonresponse to peginterferon therapy to receive 12 or 16 weeks of sofosbuvir/ribavirin. The primary endpoint in both studies was SVR at 12 weeks after therapy ended.

In patients for whom peginterferon therapy was not an option, SVR was 78% for treatment with sofosbuvir/ribavirin compared with 0% for placebo (P<0.001). In previously treated patients, SVR was 50% for 12 weeks of therapy versus 73% for 16 weeks (P<0.001). SVR rates were lower for patients with genotype 3 versus genotype 2 in both treatment-naive patients (61% vs. 93%) and treatment-experienced patients who received therapy for 12 weeks (30% vs. 86%) or 16 weeks (62% vs. 94%).

Comment: Oral sofosbuvir plus ribavirin is effective in patients with HCV genotypes 2 or 3 for whom peginterferon-based therapy is not an option or was previously ineffective. Of note, these sustained virologic response rates for sofosbuvir plus ribavirin are comparable to or higher than those previously reported for therapy with peginterferon plus ribavirin in this population.

Offered on the blog today are a few studies that look at the risk for developing liver cancer in people who are - or who have been - infected with chronic hepatitis C. The CDC reported hepatitis C is the leading cause of liver cancer which is the fastest rising cause of cancer-related death in the U.S. Without a doubt this disease can lead to serious health problems including liver damage, cirrhosis, liver cancer and liver failure.

In the United States the CDC has implemented screening strategies to identify people at high risk for hepatitis C. Included in the risk group are people born between 1945 and 1965 - age 47 to 67, who currently account for about 75% of the estimated 2.7 and 3.9 million people infected with the virus.

I often ask myself why people forgo HCV testing if they fall into this high risk population. Most people would agree, preventive strategies for cancer or liver damage are worth the time it takes for a routine blood test.

Additionally a large portion of people are unaware they are infected. These people are in need of clinical evaluation and counseling including prevention strategies; using alcohol, supplements, over-the-counter medications or prescription drugs can cause additional liver damage.

Alcohol And HCV

Older studies have confirmed in patients with hepatitis C heavy alcohol intake contributes to HCV-associated liver disease and can cause significantly more liver scarring or cirrhosis, a more recent study has shown even moderate alcohol increases the risk for liver-related mortality. Last month in the medical journal Alimentary Pharmacology & Therapeutics, researchers concluded; Although chronic hepatitis C is associated with increased risks for overall and liver-related mortality, these risks are even higher for patients consuming moderate and excessive amounts of alcohol. Here is a comment from the study's lead author Zobair Younossi; For instance, the risk of liver-related death among people with hepatitis C who averaged two or fewer drinks a day was 74 times that of similar people without hepatitis C. Check out the interview here.

Disease Progression

Medscape reported: Out of 100 people that contract the infection, 75–85 people will develop chronic infection, 60–70 people will develop chronic liver disease, five to 20 people will develop cirrhosis over the course of their chronic infection and one to five people will die of complications including hepatocellular carcinoma (HCC). The good news is that the overall percentage of people with HCV who develop cirrhosis or liver cancer is low, unless that person is you, then its at 100%.

Liver Cancer Without Cirrhosis?

In the June 2013 issue of American Journal of Roentgenology researchers investigated liver cancer in patients with chronic HCV - without advanced fibrosis or cirrhosis.

OBJECTIVE. The objective of our study was to describe the cross-sectional imaging appearance of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection in the absence of advanced fibrosis and cirrhosis.

MATERIALS AND METHODS. This study is a retrospective review of our surgical database to identify patients with chronic HCV infection and HCC who underwent hepatectomy and who had undergone preoperative CT or MRI. Only patients with a Metavir fibrosis score of F0, F1, or F2 on pathology were included. Patients with hepatitis B virus coin-fection or other causes of chronic liver disease and patients with histopathologic evidence of advanced fibrosis or cirrhosis (Metavir scores F3 and F4) were excluded. Contrast-enhanced CT or MRI examinations performed within 2 months before surgery were reviewed for the number, size, and location of tumors; tumor enhancement characteristics; and presence of macrovascular invasion.

RESULTS. Two hundred forty-five resections of HCC in patients with HCV were performed in our institution from 1987 to 2012. Of this group, 26 patients (10.6%) had a Metavir fibrosis score of F0, F1, or F2; of those patients, 19 (18 men and one woman; 18 non-Asian patients and one Asian patient; mean age, 64 years) had imaging studies available for review. Twenty-one HCCs (mean size, 4.5 cm; range, 0.9-14.8 cm) were evaluated at imaging. Typical wash-in and washout characteristics were seen in 16 of 19 viable lesions (84.2%). The remaining two HCCs were completely necrotic after transarterial chemoembolization. Eighteen patients had a solitary tumor. Most tumors (15/21, 71.4%) developed in the right hepatic lobe.

CONCLUSION. HCC can develop in patients with chronic HCV without advanced fibrosis or cirrhosis, most frequently in older non-Asian men, and usually appears as a large solitary tumor with a typical wash-in-washout enhancement pattern.

Liver Cancer With Cirrhosis After Successful HCV Therapy

Last month in Clinical Infectious Diseases, researchers concluded: The risk for HCC, liver decompensation, and death in patients with liver cirrhosis related to HCV was markedly reduced after SVR, but a long-term risk of developing HCC remains for up to 8 years.

This month the in-depth clinical information website, Healio.com featured the study:

HCC risk persists 8 years after HCV eradication

May 9, 2013

The long-term risk for hepatocellular carcinoma among patients with hepatitis C remains up to 8 years after sustained virological response to antiviral therapy, researchers reported in Clinical Infectious Diseases.

The number of patients with cancer was too low to draw any firm conclusion, but it was nevertheless somewhat surprising that the risk remained for such a prolonged time period,” Soo Aleman, MD, PhD, of the departments of gastroenterology and hepatology and infectious diseases at Karolinska Institutet in Stockholm, told Infectious Disease News.

“We need to know how long this risk persists and which subgroups of patients are at the highest risk after achieving sustained virological response (SVR). Future studies are needed to answer these questions.”

Aleman and colleagues conducted a prospective study that included patients who had HCV-related cirrhosis.

Among the 351 patients, 110 reached SVR, 193 did not and 48 were untreated. The study was initiated in 2001 and the patients were followed for a mean of 5.3 years.

Six patients who achieved SVR developed hepatocellular carcinoma (HCC), for an incidence of 1 per 100 person-years. Two patients were diagnosed within a year after achieving SVR at 0.5 and 7.7 months, and the remaining four were diagnosed at 2.4, 7.4, 7.4 and 7.6 years.

All of the patients were tested for HCV RNA at HCC diagnosis, and all were negative.

Among patients who did not achieve SVR or who were untreated, the risk for HCC was higher. The risk for any liver-related complication, liver-related death or overall death was lower among patients who achieved SVR. These differences were similar after controlling for alcohol use, age, sex and diabetes.

“Patients who have liver cirrhosis prior to the eradication of HCV should continue to undergo surveillance with ultrasound regularly for early detection of hepatocellular carcinoma,” Aleman said.Soo Aleman, MD, PhD, can be reached at Department of Gastroenterology and Hepatology, and Infectious Diseases, Karolinska University Hospital at Karolinska Institute, 171 76 Stockholm, Sweden; email: soo.aleman@ki.se.

According to WHO in 25 % of liver cancer patients, the underlying cause is hepatitis C. Long-term management of chronic hepatitis C infection for patients with cirrhosis include routine screening for liver cancer. These tests might mean an
ultrasound twice a year, and twice-yearly measurements of alpha-fetoprotein (AFP) levels in the blood, which is a
liver-cancer marker.Get TestedIf any of the risk factors mentioned in this article pertain to you, I urge you to please consider the CDC's recommendation and get tested once for hepatitis C. If the test is positive additional testing is needed.

Today's data show that even among young people who get tested positive, only about half had follow-up tests to see if they were still infected. That's what you need to get appropriate care and treatment. Right now there are better Hepatitis C treatments available than ever and there are more treatments coming in the coming year. So confirming that someone is more infected is more important than ever. Not everyone with Hepatitis C will need treatment, but everyone with Hepatitis C should be linked to care so that they can monitor how their liver is doing, determine when and if treatment is warranted, avoid things like excess alcohol which can damage their liver, and avoid medications that could also damage their liver as well as getting vaccinated against hepatitis b to protect their liver. Liver disease is something which is causing an increasing number of deaths, and many of those deaths could be prevented with the current treatments and with preventive actions that people can take if, but only if, they know that they're infected. Today CDC is also issuing updated guidance for doctors and other health care providers about how to test for Hepatitis C and how to provide follow-up.

Need To Talk To Someone ?

Help is available, recently "Project Inform" announced the launch of a new national helpline, 877-HELP-4-HEP (877-435-7443), run by and for people affected by hepatitis C.

ORLANDO – Both 12- and 24-week regimens of an investigational interferon-free therapy for hepatitis C were associated with high sustained virological response rates at 12 weeks post treatment in a phase II study of patients with hepatitis C virus genotype 1 who had baseline characteristics associated with poor response to interferon-based therapies.

The Aviator trial assessed the safety and efficacy of various dosing regimens and combinations of three AbbVie investigational direct-acting antivirals (DAAs) with or without ribavirin, including the potent hepatitis C virus (HCV) protease inhibitor ABT-450 dosed with 100 mg of ritonavir (ABT-450/r, dosed at 100 or 150 mg daily), the NS5A inhibitor ABT-267 (25 mg daily), and the non-nucleoside NS5B inhibitor ABT-333 (400 mg twice daily). A total of 247 patients were included in the subanalysis, Dr. Nunes reported at the meeting.

The regimen that included all three investigational drugs and ribavirin, known as 3 DAA/RBV, was associated with sustained virological response rates of 99% and 93% at 12 weeks in treatment-naive patients and previous peg-interferon/ribavirin (peg-IFN/RBV) null responders, respectively, said Dr. Nunes, who is clinical associate professor of medicine in the University of Pennsylvania Health System, and section chief of gastroenterology at Pennsylvania Hospital, Philadelphia.

In the current analysis, high sustained virological response rates at 12 weeks (SVR12) were also achieved in the 247 patients with chronic HCV genotype 1, including 159 treatment-naive and 88 previous peg-IFN/RBV null responders, who were assigned to 12 or 24 weeks of 3 DAA/RBV. The virological response rates were 99% and 93% for the treatment-naive 12- and 24-week groups, respectively, and 93% and 98% for the null responder 12- and 24-week groups.

The high responses occurred regardless of treatment duration, age, race, ethnicity, BMI, Homeostatic Model of Assessment–Insulin Resistance (HOMA-IR), IL-28B host genotype, or baseline viral load. The rates did not differ significantly on any comparison made in treatment-naive patients or previous null responders, he said.

In the treatment-naive patients, no breakthroughs occurred, although 1% of those in the 12-week treatment arm relapsed, and 3% of the 24-week treatment group relapsed.

In the null responder group, no relapses occurred, but breakthroughs occurred in 7% of those in the 12-week treatment arm, and in 2% of the 24-week treatment arm, he said.

Treatment was safe and generally well tolerated. Four patients discontinued treatment due to drug-related adverse events, most commonly fatigue (in 32.7% and 23.9% of treatment-naive and null responders, respectively) and headache (31.4% and 30.7%, respectively).

One patient had a serious adverse event (arthralgia) considered to be possibly related to the study drug regimen.

Because ribavirin was included in the treatment regimens, it is impossible to tease out whether the adverse events were associated with that drug or with the investigational DAAs, Dr. Nunes noted.

Patients included in the study were noncirrhotic adults aged 18-70 years with a BMI between 18 and 38 kg/m2, and HCV genotype 1.

"The overall efficacy was excellent irrespective of the baseline grouping. So black race, Hispanic/Latino ethnicity, age greater than 50, BMI over 30, male gender, HOMA-IR greater than 3, IL-28B non-cc genotype, and viral load greater than 7 logs all had very high SVR12 response rates," Dr. Nunes said.

The safety and efficacy of this interferon-free 3 DAA/RBV therapy will be further explored in phase III studies, he said.

Dr. Nunes has received grant or research support from Merck, Abbott Laboratories, and Roche Pharma AG.

May 24, 2013
The risks for neuropsychiatric adverse events among patients with hepatitis C virus being treated with direct-acting antivirals appear minimal, but the risks for drug-drug interactions are high, according to recent study results.

Researchers conducted a literature search of PubMed from 2000 to April 2013 using the search terms, “hepatitis C” and “boceprevir” or “telaprevir,” along with “mental disorders,” “psychotropic drugs” and “drug interactions.” The analysis was designed to evaluate studies on neuropsychiatric adverse effects as a result of direct-acting antivirals (DAAs) and drug-drug interactions (DDIs) involving psychotropic medications and DAAs among hepatitis C virus (HCV) patients.

HCV Education
Review learning activities, editorials, with new data about interferon-free regimens approved for HCV, as well as investigational drugs still in the pipeline. Links are provided to support, patient friendly information, clinical trials, peer-reviewed journals, videos, conferences with commentary, all updated on a continuous basis.

Users can search for a hepatitis C clinical trial by category (genotype), or learn how to evaluate a clinical trial and become familiar with commonly used terms. HCV Advocate offers an easy to navigate HCV Medications Blog as well, organized by HCV genotype

View each rebuttal and all ongoing media coverage. In June the HCV community was blindsided when an article with a somewhat "clickbait" headline was released by The Guardian. The Guardian reported on a systematic review published by the Cochrane Collaboration that suggested achieving SVR (cure) for patients using hepatitis C direct-acting antivirals (DAAs) doesn't correlate with any long term benefits.

The controversy over expensive new drugs for hepatitis C
Link to research and news articles addressing the high cost of hepatitis C drugs; insurance restrictions - private insurers/Medicaid - and availability of generic versions/India, Egypt and other lower-income countries or through online "buyers clubs"

Liver Cancer After Treatment For Hepatitis C
​Research demonstrates that while SVR markedly reduced liver-related complications and liver cancer, some long-term risk for liver cancer remained in those who were cured of Hepatitis C. But after direct-acting antiviral therapy does the risk of developing liver cancer increase?

Meeting Updates

April 19-23
The European Association for the Study of the Liver (EASL) International Liver Congress (ILC 2017)

Merck today announced its strategic decision to discontinue the development of the investigational combination regimens MK-3682B (grazoprevir/ruzasvir/ uprifosbuvir) and MK-3682C (ruzasvir/uprifosbuvir) for the treatment of chronic hepatitis C virus (HCV) infection. This decision was made based on a review of available Phase 2 efficacy data and in consideration of the evolving marketplace and the growing number of treatment options available for patients with chronic HCV infection

Two HCV Drugs to Be Discontinued
The Food and Drug Administration (FDA) announced that Rebetol(ribavirin; Merck) capsules and PegIntron (peginterferon alfa-2b; Merck) for Injection are being discontinued. The decision is business-related and not due to safety or efficacy issues with the drugs.

Rebetol is a nucleoside analogue indicated for chronic hepatitis C in combination with interferon alfa-2b (pegylated and nonpegylated), in patients ≥3 years of age with compensated liver disease. It is supplied as 200mg capsules in 56-, 70-, and 84-count bottles. The Rebetol discontinuation is effective February 1, 2016.
PegIntron is an antiviral indicated for treatment of chronic hepatitis C in patients with compensated liver disease. It is supplied as 50mcg/0.5mL, 80mcg/0.5mL, 120mcg/0.5mL, and 150mcg/0.5mL single-use vials and single-use pre-filled pens. No effective date is available for the PegIntron discontinuation.

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